This study was designed to examine generally the influence of the gastrointestinal tract upon the insulin response to ingested glucose, and specifically the role of one or more gastrointestinal hormones in the process of insulin secretion. The study is being applied to altered physiologic states, including aging diabetes mellitus, and obesity. The observation that the response of the endocrine pancreas to ingested glucose is greater than its response to glucose administered intravenously, is well established. The physiologic and biochemical etiology of this finding, however, has remained open to debate and investigation. Similarly, the significance of this process in pathologic states is unknown. While gastrointestinal hormones have been suggested as possible mediators of the phenomenon, until recently none has been clearly shown to play a critical role. The development of a sophisticated laboratory technique for studying this process, and the avilability of a specific assay for a newly discovered gastrointestinal peptide which appears a likely candidate as the sought-after mediator, have provided the essential means of investigating this process.